亚低温脑保护的分子生物学机制研究进展

低温是目前公认最有效的神经保护疗法。随着血管内导管降温疗法最新进展,心脏停搏后低温试验成功,低温疗法脑保护机制研究重新引起关注。通常,低温分为轻度低温(33~35℃)、中度低温(28~32℃)、深度低温(17~27℃)和超深度低温(2~16℃)[1]。20世纪90年代,临床应用28~35℃亚低温治     

亚低温治疗缺血性脑病的研究进展

国际上一般将低温分为轻度低温(33~35℃)、中度低温(28~32℃)、深度低温(17~27℃)和超深低温(2~16℃),前两者合称为亚低温。研究表明,在脑外伤、脑出血、脑缺血等多种脑部疾病中亚低温能够通过多种途径发挥脑保护作用[1-2]。缺血性脑病为脑部疾病中的一大类,是神经科的常见病和多发病,致残率极高,严重威胁人类的健康与生存,在该类疾病的治疗中亚低温以其独特的优势而倍受医学工作者的关注。1亚低温应用于脑领域的发展史1945年,Fay首先报道了应用中度低温治疗颅脑损伤患者。1950年,Mohri报道了深度低温对动物的全脑缺血有保护作用。此后,Dr…     

神经内科使用亚低温治疗仪的护理体会

亚低温(mild hypothermia,MHT)技术治疗急性脑血管病和急性颅脑损伤逐渐受到重视.电子冰帽对脑部进行选择性降温,使脑温迅速下降并维持在亚低温水平(33～35℃),有利于减少低温对机体其他脏器的不良影响.     

亚低温疗法对颅脑损伤脑保护机制的研究进展

自1987年Busto等]首次提出了亚低温（32～35℃）脑保护的概念后,亚低温在脑复苏、颅脑外伤及脑梗死治疗方面均取得了显著成绩。但其对脑保护的机制尚不明确,为了进一步探讨其对颅脑损伤脑保护的治疗作用,现将亚低温疗法对颅脑损伤的保护机制综述如下。     

轻度脑低温治疗脑出血临床观察(附34例报告)

全身亚低温(32～34℃)技术对脑缺血、颅脑损伤有明显疗效已有较多报道，而对于脑出血的亚低温治疗报道较少，尤其是局部亚低温(轻度脑低温)治疗脑出血的临床效果。1998年10月至2003年6月，我们对34例重症脑出血患者采用轻度脑低温治疗，疗效满意。现报告如下。     

急性卒中亚低温疗法及其抑制炎症反应因子研究进展

20世纪50年代,国外学者将深低温（〈28℃）用于心血管外科手术时脑和其他重要器官的保护,效果不错。但由于低温引起的严重不良反应,如心律失常、凝血功能障碍和肺部感染等,限制了其在临床上的应用。20世纪80年代,人们又发现,轻度低温（又称亚低温,32—35℃）同样有很好的脑保护效果,并且不良反应较小,从此推动了低温治疗脑卒中的研究。随着对亚低温研究的不断深入,人们发现亚低温对脑缺血后患者有许多益处。本文就急性卒中亚低温疗法的作用及其抑制炎症反应相关因子的研究概况综述如下。     

亚低温对大鼠脑微血管内皮细胞中P-糖蛋白表达的影响

目的探讨亚低温对大鼠脑微血管内皮细胞中P-糖蛋白表达的影响。方法将原代分离的大鼠脑微血管内皮细胞按培养温度分三组：37℃组、35℃组、32℃组,并在相应温度的培养箱下培养5d。运用免疫细胞方法检测大鼠脑微血管内皮细胞中P-糖蛋白,采用Westernblot方法测定各组细胞中P-蛋白的含量变化。结果37℃组细胞P-糖蛋白表达明显高于亚低温的另外两组（P均〈0．01）,35℃组细胞P-糖蛋白表达高于32℃组（P〈0．05）。结论亚低温情况下对大鼠脑微血管内皮细胞中P-糖蛋白表达量有明显影响,从而对药物药动学和药效学产生影响。     

选择性亚低温治疗对颅脑损伤患者免疫功能及预后的影响

20世纪90年代以来，大量动物实验和临床应用研究证明亚低温具有脑保护作用。但通过全身性降温来进行亚低温治疗有引起心律不齐、凝血障碍、免疫功能障碍、感染及复温休克等并发症的可能，因此，一些学者提出了“选择性脑部亚低温”的概念，即通过某种方法进行脑部的选择性降温，达到脑部的亚低温状态(30℃～35℃)。动物实验结果显示，选择性脑部亚低温同样能显著减轻脑缺血及实验性脑损伤动物的继发性脑损害和脑水肿，保护神经功能，减少有害物质的生成，提高存活率。2001年1月至2003年5月，我们检测了81例急性颅脑损伤患者的免疫功能，并将40例重型颅脑损伤患者随机分为选择性亚低温治疗组和常规治疗组，观察选择性亚低温对其免疫功能及预后的影响。现报告如下。     

亚低温对静脉窦血栓形成合并脑病患者脑保护作用的初步研究

目的 初步探讨亚低温辅助治疗对静脉窦血栓形成导致颅内高压合并脑病患者的脑保护效果.方法 回顾性分析14例静脉窦血栓形成颅内高压合并脑病患者的临床资料.所有患者均接受了静脉窦内接触性溶栓结合机械碎栓治疗,同时采用脱水、降颅压等多种药物治疗.对发生脑庙后的6例患者,行开颅清除血肿和（或）单纯去骨瓣减压术.对7例患者（亚低温组）采用亚低温辅助治疗的方法,控制目标肛温在35℃,平均持续（4 ±2）d;对另外7例（非亚低温组）常规控制目标肛温〈 38℃.比较两组患者短期和长期神经系统功能的情况、疾病转归和预后.结果 ①降温24 h时,亚低温组的肛温平均为（35.2±0.9）℃,非亚低温组为（37.1±0.5）℃.②亚低温组3例患者存活且恢复良好,3个月格拉斯哥预后评分（GOS）为（27±2.1）分,死亡4例;非亚低温组死亡6例,存活1例,GOS为4分.亚低温组死亡比例为4/7,非亚低温组为6/7,P=0.559.结论 重症静脉窦血栓形成导致颅内高压合并脑病患者的病死率高,亚低温辅助治疗可能具有一定的脑保护作用,从而降低患者的病死率.     

全身亚低温对脑缺血保护作用的实验研究进展

在缺血性卒中治疗研究中,脑保护越来越受到重视。其中全身亚低温(32～35℃)方法的显著保护作用及易实施的特点,显示有良好的应用前景。亚低温脑保护的可能机理是降低代谢,抑制神经毒性物质的过度释放,从而保护血脑屏障,减轻脑水肿及改善缺血后低灌注,防止过灌注损伤,以挽救受影响的神经元,达到脑保护的目的。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.